Vascular tone and blood pressure control during exercise

描述（由申请人提供）：运动期间血压的调节对于确保重要器官的充分灌注和骨骼肌的锻炼至关重要。有人认为，由于运动期间绝大多数心输出量都流向活跃的骨骼肌，因此运动骨骼肌时的血管收缩对于维持血压至关重要。事实上，申请人之前的出版物证明了即使在繁重的工作负荷下，在锻炼骨骼肌时也存在显着的α肾上腺素能受体介导的血管收缩。刺激血管平滑肌中的非肾上腺素受体，例如嘌呤能 (P2X)、神经肽 Y (NPY Y1) 和内皮素 (ETA) 受体也可以在静息骨骼肌的脉管系统中产生血管收缩，但这些受体对运动骨骼肌中强直性血管收缩的贡献仍然很大程度上未知。本申请中的初步数据清楚地证明了 P2X 和 NPY Y1 受体介导的血管收缩在骨骼肌锻炼中的潜力。尽管在活跃的骨骼肌中存在交感血管收缩，但申请人先前的工作证明运动会导致骨骼肌脉管系统中α肾上腺素能受体反应性的减弱。尽管本申请中描述的初步研究提供了一个有趣的建议，即骨骼肌中的 P2X 和 NPY Y1 受体反应性在运动期间也会减弱，但血管平滑肌中的非肾上腺素受体是否表现出类似的从休息到运动的反应性降低仍有待确定。该提议的总体假设是非肾上腺素受体有助于骨骼肌运动时的血管收缩。提出了两个具体目标： 1. 确定非肾上腺素受体对骨骼肌运动中血管收缩的贡献。 2. 检查休息和运动时骨骼肌脉管系统中的非肾上腺素受体反应性。拟议研究的主要优势是能够研究有意识、运动的动物的基本生理机制。实验方案的一个独特方面是能够将激动剂和拮抗剂递送到离散的血管床而不改变其他血管床的动脉压或血流。拟议的研究将提供有关动态运动期间调节活跃骨骼肌血流的生理机制的有价值的新信息。这是一个非常重要的问题，可能对患有周围血管疾病的个体产生重要影响。

DESCRIPTION (provided by applicant): The regulation of blood pressure during exercise is of paramount importance to ensure adequate perfusion of vital organs and exercising skeletal muscle. It has been argued that because the vast majority of cardiac output during exercise is directed toward active skeletal muscle, vasoconstriction in exercising skeletal muscle is of primary importance in maintaining blood pressure. Indeed, previous publications by the applicant demonstrated substantial alpha adrenergic receptor mediated vasoconstriction in exercising skeletal muscle even at heavy workloads. Stimulation of non-adrenergic receptors in vascular smooth muscle, such as purinergic (P2X), neuropeptide Y (NPY Y1), and endothelin (ETA) receptors can also produce vasoconstriction in the vasculature of resting skeletal muscle, but the contribution of these receptors to tonic vasoconstriction in exercising skeletal muscle remains largely unknown. Preliminary data in this application clearly demonstrate the potential for P2X and NPY Y1 receptor mediated vasoconstriction in exercising skeletal muscle. Despite the existence of sympathetic vasoconstriction in active skeletal muscle, previous work by the applicant demonstrated that exercise produces an attenuation of alpha adrenergic receptor responsiveness in the vasculature of skeletal muscle. It remains to be determined whether non-adrenergic receptors in vascular smooth muscle exhibit a similarly reduced responsiveness from rest to exercise although pilot studies described in this application provide an intriguing suggestion that P2X and NPY Y1 receptor responsiveness in skeletal muscle is also attenuated during exercise. The overall hypothesis underlying this proposal is that non-adrenergic receptors contribute to vasoconstriction in exercising skeletal muscle. Two specific aims are proposed: 1. To determine the contribution of non-adrenergic receptors to vasoconstriction in exercising skeletal muscle. 2. To examine non-adrenergic receptor responsiveness in the vasculature of skeletal muscle at rest and exercise. A major strength of the proposed studies is the ability to study basic physiological mechanisms in conscious, exercising animals. A unique aspect of the experimental protocols is the ability to deliver agonists and antagonists to a discrete vascular bed without altering arterial pressure or blood flow in other vascular beds. The proposed studies will provide valuable new information regarding the physiological mechanisms by which blood flow to active skeletal muscle is regulated during dynamic exercise. This is an issue of fundamental importance that may have important implications for individuals with peripheral vascular disease.